Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of ARDS (RAPA-CARDS)

Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

Study Overview

• Status: Withdrawn
• Conditions: Respiratory Failure; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Sars-CoV2
• Intervention / Treatment: Drug: Placebo; Drug: Rapamycin

Detailed Description

This is a single center, double-blind, placebo-controlled, randomized clinical trial in which each participant, after admission to hospital with a diagnosis of mild to moderate COVID-19 infection, will be administered either a dose of rapamycin or the placebo daily. Each subject will receive the assigned treatment until hospital discharge or death. Evaluations will be performed at the beginning of the clinical trial and then daily up to 4 weeks.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Audie L Murphy Memorial Veterans Hospital
    • San Antonio, Texas, United States, 78228
      • University Hospital System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Over 60 years of age clinically judged to require hospitalization
2. SARS-CoV2 infection documented by positive RT-PCR nasopharyngeal swab

3. Mild to Moderate clinical status defined as clinical symptoms with or without pneumonia on imaging, with or without fever who are judged to require hospital admission

   1. Elevated ferritin
   2. Lymphopenia
   3. Bilateral opacities on chest x-ray
   4. Low pro-calcitonin
   5. Clinical signs suggestive of symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea or moderate illness with CoVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, heart rate ≥ 90 beats per minute.

Exclusion Criteria:

1. Known or suspected allergy to RAPA
2. High pro-calcitonin
3. SARS-CoV2 documented by negative RT-PCR nasopharyngeal swab
4. Treatment with contraindicated concomitant medications: currently receiving immunosuppressants, including steroids, prior to enrollment, or with immunomodulators or immunosuppressant drugs, including but not limited to Inter leukin (IL)-6 inhibitors, Tumor necrosis factor (TNF) inhibitors, anti-IL-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or 30 days (whichever is longer) prior to randomization.
5. Currently receiving immunosuppressants, including steroids, prior to enrollment
6. Serious underlying disease including but not limited to cardiac, pulmonary, renal, hepatic (bilirubin >1.5x Upper normal limit (ULN) or Aspartate Aminotransferase (AST)>ULN but bilirubin ≤ ULN), endocrine (diabetes) or psychiatric disorders judged to be at risk in participating by the inpatient attending physician or team
7. Suspected or confirmed history of alcohol or substance abuse disorder
8. Having participated in other drug trials in the past month
9. Deemed otherwise unsuitable for the study by researchers
10. Clinically judged to not require hospital admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Administration of placebo daily during hospitalization	Drug: Placebo; Administration of investigational drug placebo for up to 4 weeks while hospitalized; Other Names: Placebo Tablet or oral solution
Active Comparator: Rapamycin; Administration of rapamycin (sirolimus) 1mg daily during hospitalization	Drug: Rapamycin; Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized; Other Names: Sirolimus; Rapamune; RAPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival rate	The proportion of participants who survive without respiratory failure	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Status assessed by the World Health Organization (WHO) scale	The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8	Baseline to 4 weeks
Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale	An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)	Baseline to 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Total number of deaths during the study period	4 weeks
Duration of ECMO	Number of days on ECMO	Up to 4 weeks
Duration of supplemental oxygen	Number of days participants are on supplemental oxygen	Up to 4 weeks
Length of hospital stay	Days of hospitalization	Up to 4 weeks
Length of time to SARS-CoV2 negativity	Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)	Up to 4 weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: The Claude D. Pepper Older Americans Independence Centers
• Investigators: Principal Investigator: Dean L Kellogg, MD, PhD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; COVID-19; Syndrome; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: HSC20200489H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD, all IPD that underlie results in a publication will be shared.
• IPD Sharing Time Frame: Data will become available at study completion at the time of journal publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No